Inflammasomes in the lung

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HighlightsActivation of the inflammasome plays a critical role in the innate immune response against noxious stimuli in the lung.Excessive activation of the inflammasome may be associated with the development of chronic lung diseases.Inflammasome-targeted, site-specific therapeutics may be beneficial in suppressing inflammasome-associated disease.Innate immune responses act as first line defences upon exposure to potentially noxious stimuli. The innate immune system has evolved numerous intracellular and extracellular receptors that undertake surveillance for potentially damaging particulates. Inflammasomes are intracellular innate immune multiprotein complexes that form and are activated following interaction with these stimuli. Inflammasome activation leads to the cleavage of pro-IL-1β and release of the pro-inflammatory cytokine, IL-1β, which initiates acute phase pro-inflammatory responses, and other responses are also involved (IL-18, pyroptosis). However, excessive activation of inflammasomes can result in chronic inflammation, which has been implicated in a range of chronic inflammatory diseases. The airways are constantly exposed to a wide variety of stimuli. Inflammasome activation and downstream responses clears these stimuli. However, excessive activation may drive the pathogenesis of chronic respiratory diseases such as severe asthma and chronic obstructive pulmonary disease. Thus, there is currently intense interest in the role of inflammasomes in chronic inflammatory lung diseases and in their potential for therapeutic targeting. Here we review the known associations between inflammasome-mediated responses and the development and exacerbation of chronic lung diseases.

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